C. Godfraind et Jp. Coutelier, MORPHOLOGICAL ANALYSIS OF MOUSE HEPATITIS-VIRUS A59-INDUCED PATHOLOGYWITH REGARD TO VIRAL RECEPTOR EXPRESSION, Histology and histopathology, 13(1), 1998, pp. 181-199
Mouse hepatitis virus, strain A59 (MHV-A59), is a coronavirus that tri
ggers in susceptible mice a wide variety of pathologies, including hep
atitis, thymus involution, B lymphocyte polyclonal activation and, aft
er intra-cerebral inoculation, transient demyelination. One receptor t
hat mediates entry of the virus into target cells has been identified:
it is a glycoprotein of the carcinoembryonic antigen family, called B
gp1a. The availability of antibodies recognizing this molecule permits
the analysis of its cellular expression and of the relationship betwe
en receptor expression and pathology induced by the virus. Bgp1a is fo
und on epithelial and endothelial cells as well as on B lymphocytes an
d macrophages. In the liver, Bgp1a expression correlates well with inf
ection of hepatocytes and endothelial cells, leading to the developmen
t of hepatitis. However, other cells expressing this molecule, such as
central nervous system endothelial cells, are not infected by the vir
us. This observation may explain how the blood-brain barrier prevents
dissemination of MHV-A59 from the general circulation into the brain.
Thymic atrophy results from apoptosis of immature double-positive T ly
mphocytes which might be caused indirectly by infection of a small pro
portion of thymus epithelial cells that express Bgp1a rather than by i
nfection of T cells that do not express the receptor. Finally, polyclo
nal activation of B lymphocytes, leading to increased secretion of ant
ibodies of the IgG2a isotype, involves a cascade of events, including
cytokine secretion, that may result from the interaction of MHV-A59 wi
th B cells and macrophages that express Bgp1a. Therefore, after viral
infection, cellular expression of Bgp1a may have different results: ce
ll lysis; alteration of cellular functions that may lead to indirect d
eath of other cell types, or resistance to infection.